Sensory experience early in life leads to the establishment and refinement of synaptic connections, through cellular mechanisms that are not yet understood. Electron microscopic immunocytochemical (EM-ICC) studies have provided information about the molecular composition of developing cortical synapses. However, it has been difficult to correlate this information with the results of electrophysiological studies. The proposed research uses a novel combination of electrophysiology, tract-tracing and EM-ICC to examine the molecular composition of physiologically/anatomically characterized synapses in somatosensory cortex. In particular, recent evidence suggests that the activity of central nicotinic acetylcholine receptors is important for the early development of excitatory cortical synapses. The presence of these receptors will be assessed in synapses between identified cortical neurons where the maturity of the connection has been determined physiologically. In a related study, the use of anatomical tract tracers in conjunction with EM-ICC will allow comparison of intracortical to thalamocortical connections. The research is expected to extend current knowledge of the mechanisms by which the cholinergic system modulates the formation of excitatory synapses. These mechanisms are likely to underlie the influence of states of sleep, wakefulness, attention and arousal on the processes of learning and memory formation.